Idiopathic ventricular fibrillation, not Brugada type
-Rare cardiac disease
-Rare genetic disease
Comment:
VF1 is a sub-type idiopathic ventricular fibrillation, not Brugada type (Phenodis:2422). For symptom annotation please refer to idiopathic ventricular fibrillation, not Brugada type.
Ventricular fibrillation (VF) is said to cause more than 300,000 sudden deaths each year in the US alone. In approximately 5 to 12% of cases, there are no demonstrable cardiac or noncardiac causes to account for the episode, ... Ventricular fibrillation (VF) is said to cause more than 300,000 sudden deaths each year in the US alone. In approximately 5 to 12% of cases, there are no demonstrable cardiac or noncardiac causes to account for the episode, which is therefore classified as idiopathic ventricular fibrillation (IVF). Patients with a distinct form of VF called Brugada syndrome (see 601144) present with a characteristic electrocardiographic pattern, with right bundle branch block (RBBB) and elevation of ST segment in leads V1 to V3 and may account for 40 to 60% of all IVF cases (review by Chen et al., 1998). Mutations in the SCN5A gene were identified in patients with Brugada syndrome-1 (601144). McRae et al. (1974) described a family in which 3 brothers had syncopal attacks and died suddenly at ages 17, 12, and 12 years. Autopsy in 2 of them showed no abnormality. A fourth brother had syncopal episodes and proved paroxysmal ventricular fibrillation. Important electrocardiographic changes were short PR interval and prominent gamma wave. Fibrillation was induced by stressful emotional stimuli, but could not be induced by exercise. Propranolol was found to be effective prophylactic medication. The mother had experienced 25 episodes of syncope between ages 15 and 25. Each episode was precipitated by an emotionally stressful event causing fright or anger. The mother, like her son, had a short PR interval. Because of the EKG changes, this family may have had a repolarization abnormality. Viskin and Belhassen (1990) reviewed the literature dealing with sudden death and identified 19 articles in which ostensibly healthy patients with documented VF unrelated to any known cardiac or noncardiac etiology were reported. Fifty-four patients fulfilled the criteria for IVF. The mean age of patients in studies that reported age data was 36 years, with a male-to-female ratio of 2.5 to 1. Over 90% of the patients required resuscitation, while syncope due to nonsustained VF occurred in the rest. Diagnosis of VF was preceded by syncope in one-fourth of the patients. Holter monitoring and exercise stress tests were often unrewarding. Available electrophysiologic data revealed a 69% inducibility rate of sustained ventricular tachyarrhythmias using nonaggressive protocols of ventricular stimulation in most cases. Induced tachyarrhythmias were poorly tolerated, and were mostly of polymorphic configuration. Class IA antiarrhythmic agents were highly effective in preventing reinduction of these arrhythmias. Available figures suggested an 11% rate of sudden death with 1 year of diagnosis. Appropriate antiarrhythmic therapy appeared to improve prognosis. The authors concluded that IVF represents an underestimated cause of sudden cardiac death in ostensibly healthy patients.
Akai et al. (2000) described a novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome (600163.0014).
- Associations Pending Confirmation {2:Bezzina et al. (2010)} performed a genomewide association ... Akai et al. (2000) described a novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome (600163.0014). - Associations Pending Confirmation {2:Bezzina et al. (2010)} performed a genomewide association study for ventricular fibrillation complicating acute myocardial infarction in a set of 972 individuals with a first acute myocardial infarction, 515 of whom had ventricular fibrillation and 457 of whom did not, from the Arrhythmia Genetics in The Netherlands (AGNES) study. The most significant association to ventricular fibrillation was found at chromosome 21q21 (dbSNP rs2824292, odds ratio = 1.78, 95% confidence interval 1.47-2.13, p = 3.3 x 10(-10)). The association of dbSNP rs2824292 with ventricular fibrillation was replicated in an independent case-control set consisting of 146 out-of-hospital cardiac arrest individuals with myocardial infarction complicated by ventricular fibrillation and 391 individuals who survived a myocardial infarction (odds ratio = 1.49, 95% confidence interval 1.14-1.95, P = 0.004). The closest gene to this SNP is CXADR (602621), which encodes a viral receptor implicated in myocarditis and dilated cardiomyopathy and which has been identified as a modulator of cardiac conduction.